CHARACTERIZATION OF MUTANT HA-RAS GENE-EXPRESSION IN TRANSFORMED MURINE KERATINOCYTE LINES GROWN UNDER IN-VITRO AND IN-VIVO CONDITIONS

We investigated the Ha-ras and Ki-ras gene status, tumorigenicity, pat hology, line derivation, and intercellular communication of 7,12-dimet hylbenz[a]anthracene-initiated papilloma-, carcinoma-, and hyperplasti c skin-producing cell lines to further characterize them. Six of nine tumor cell lines grown in vitro expressed both mutant and normal Ha-ra s proteins, and three lines expressed only normal Ha-ras. However, whe n grown subcutaneously in nude mice, seven of the nine lines expressed both mutant and normal Ha-ras, one line expressed normal Ha-ras, and one line did not grow subcutaneously. One papilloma line, P2/15, appea red to have an inducible mutant Ha-ras gene, as it was expressed only in vivo. These findings suggest that mutant Ha-ras genes may be lost i n only a minor population of tumor lines during growth in culture. Fin ally, we found that mutant Ha-ras gene expression was strongly correla ted with tumorigenicity in nude mice and that intercellular communicat ion was strongly correlated with the derivation of the lines. (C) 1996 Wiley-Liss, Inc.